Objective To evaluate the effect of anisodamine on expression of Toll-like receptor 4 (TLR4) in the kidneys of exhausted rats.Methods Forty-eight male SD rats weighing 200-220 g were randomly divided into 3 groups:control group (group Ⅰ ) (.n =8) ; exhaustion group (group Ⅱ ) ( n =24) and anisodamine group (gronp Ⅲ) (n =16).In groups Ⅱ and Ⅲ exhaustion was induced by exhausting swimming and defined by (1) the animal sank to the bottom and stayed for＞ 10 s during swimming,(2) uncoordinated swimming,and (3) the animal lost escape/righting reflex when placed on the table In group Ⅲ intraperitoneal anisodamine 10 mg/kg was administered at 20 min before swimming.The animals were sacrificed immediately (T1 ),6 h (T2 ) and 24 h (T3 ) after exhaustion respectively.Their kidneys were obtained for detection of apoptosis and determination of TLR4 protein (by immuno-histochemical staining) and mRNA (by RT-PCR).Results Exhaustion significantly increased the number of apoptotic cells and up-regulated TLR4 protein and mRNA expression in group Ⅱ as compared with group Ⅰ,and anisodamine significantly attenuated the exhaustion-induced increase in the number of apoptotic cells and up-regulation of TLR4 protein and mRNA expression in group Ⅲ as compared with group Ⅱ.Conclusion Anisodamine can decrease apoptosis in renal cells in exhausted rats bydown-regulating TLR4 expression.

Objective To investigate the correlation between liver and spleen stiffness measured by acoustic radiation force impulse (ARFI) and hepatic venous pressure gradient (HVPG),and to evaluate its efficiency in the diagnosis of portal hypertension.Methods From April 2014 to March 2016,20 cases underwent HVPG measurement because of liver cirrhosis were enrolled.Before HVPG measurement,liver and spleen stiffness were assessed with ARFI.The correlation between HVPG and age,alanine aminotransferase (ALT),aspartate aminotransferase (AST),total hilirubin,serum albumin,platelet count,prothrombin time,aspartate aminotransferase to platelet ratio index (APRI) score,Child-Pugh score,model for end-stage liver disease (MELD) score,liver stiffness and spleen stiffness were analyzed.Pearson correlation and Spearman rank correlation were performed for statistical analysis.Results HVPG,liver and spleen stiffness were successfully measured in all 20 patients.The mean liver stiffness was (1.78±0.29) m/s,the mean spleen stiffness was (3.37±0.44) m/s and HVPG was (16.10±5.14) mmHg (1 mmHg=0.133 kPa).Age,ALT,AST,total bilirubin,serum albumin,platelet count,prothrombin time,APRI score,Child-Pugh score and MELD score were all not correlated with HVPG (all P＞0.05).But HVPG was positively correlated with liver and spleen stiffness (r=0.449,P=0.047;r=0.487,P=0.030).In the diagnosis of HVPG≥12 mmHg,the area under curve (AUC) of liver stiffness was 0.875,the optimal cut-off value was 1.77 m/s,the sensitivity was 68.6 ％ and the specificity was 100.0％.In the diagnosis of HPVG≥20 mmHg,the AUC of liver stiffness was 0.798,the optimal cut off value was 1.85 m/s,the sensitivity was 100.0％ and the specificity was 68.8％.The AUC of spleen stiffness was 0.820,the optimal cut-off value was 3.23 m/s,the sensitivity was 100.0 ％ and the specificity was 56.3％.Conclusion In patients with liver cirrhosis,liver stiffness and spleen stiffness assessed by ARFI are positively correlated with HVPG and therefore ARFI has certain application value in the noninvasive diagnosis of portal hypertension.

Objective:To analyze and compare the short-term efficacy and safety of sintilimab and tislelizumab in neoadjuvant therapy for advanced esophageal squamous cell carcinoma.Methods:The clinical data of 95 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (paclitaxel + nedaplatin) combined with immunotherapy in the Department of Thoracic Surgery of the Affiliated Hospital of North Sichuan Medical College from January 2021 to October 2022 were collected. According to the different use of immune drugs, they were divided into the sintilimab group ( n=58) and the tislelizumab group ( n=37). The objective remission rate (ORR), adverse reactions, R0 resection rate, pathological complete response (pCR) rate, etc. were analyzed and compared between the two groups after neoadjuvant therapy. Results:After 2 cycles of neoadjuvant therapy, the sintilimab group and the tislelizumab group had a similar ORR [72.4% (42/58) vs. 56.8% (21/37), χ2=2.48, P=0.115]. The main adverse reactions of the two groups of patients included gastrointestinal reactions (nausea, vomiting, diarrhea), hematological toxicity, hypothyroidism, alopecia, liver and kidney dysfunction, pneumonia, etc. The incidence of grade 3 adverse reactions was less than 15%, with no grade 4 adverse reactions. The incidence of hypothyroidism in the sintilimab group was significantly higher than that in the tislelizumab group [56.9% (33/58) vs. 16.2% (6/37) ], with a statistically significant difference ( χ2=15.45, P<0.001) ; There was no statistically significant difference in surgical resection ( χ2=1.26, P=0.661) and pCR rate [31.0% (18/58) vs. 32.4% (12/37), χ2=0.02, P=0.886] between the two groups of patients. In terms of postoperative complications, both groups of patients experienced partial pulmonary infections and anastomotic fistulas, but the incidence was relatively low [19.0% (11/58) vs. 24.3% (9/37), 3.4% (2/58) vs. 2.7% (1/37) ], with no statistically significant difference ( χ2=0.39, P=0.532; χ2<0.01, P>0.999) . Conclusion:For preoperative neoadjuvant therapy of advanced esophageal squamous cell carcinoma, the use of either sintilimab or tislelizumab in addition to chemotherapy has good short-term efficacy and safety. Thyroid function should be monitored carefully when using sintilimab.

Objective To evaluate the recurrence pattern and identify the risk factors of esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery.Methods Clinical data of 275 patients with thoracic esophageal squamous cell carcinoma treated with neoadjuvant therapy combined with surgery from December 2011 to December 2015 were retrospectively analyzed.The follow-up data of the enrolled patients were complete and analyzable.The recurrence pattern,recurrence time,recurrence location and influencing factors after neoadjuvant therapy in combination with surgery were analyzed.The recurrence rate was calculated by Kaplan-Meier method.The multivariate analysis was performed by Cox regression model.Results The median follow-up time was 32 (3-84) months,and the median time of the first recurrence was 10.6(2.0-69.1) months.The 1-,2-and 3-year recurrence rates were 32.0％,45.1％ and 52.3％,respectively.A total of 152 cases (55.3％) had recurrence.Among them,77 cases (50.6％) had local-regional recurrence (LRR),34 cases (23.4％) had distant metastasis (DM),33 cases (21.7％) had LRR+DM and 8 cases (6.0％) had recurrence in unknown site.Among the patients with LRR,lymph node recurrence was the most common (n =98,89.1％).For DM patients,lung metastasis (n =33,49.3％),liver metastasis (n=16,23.9％),bone metastasis (n=14,20.9％) and non-regional lymph node metastasis (n=14,20.9％) were commonly observed.The multivariate analysis showed that postoperative T stage (P=0.008),N stage (P＜0.001) and the number of lymph node dissection (P＜0.001) were the independent risk factors for recurrence after treatment.Conclusions The recurrence rate after neoadjuvant therapy remains relatively high for esophageal squamous cell carcinoma,and the regional lymph node is the most common site of recurrence.Postoperative pathological T staging,N staging and the number of lymph node dissection are the independent risk factors for recurrence after treatment.

Objective To evaluate the prognostic value of a novel prediction model based on fibrinogen concentration in combination with neutrophil-to-lymphocyte ratio (F-NLR score) in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant therapy and investigate their relationship with pathologic complete response (pCR).Methods Clinical data of 218 eligible ESCC patients treated with neoadjuvant therapy in the Affiliated Cancer Hospital of Zhengzhou University between 2012 and 2015 were retrospectively analyzed.The cut-off values for fibrinogen and neutrophil-to-lymphocyte ratio (NLR)were defined by the receiver operating characteristic (ROC) curve.The effects of different F-NLR scores on survival and pCR were evaluated.The survival rate was analyzed using the Kaplan-Meier method.The relationship among fibrinogen,NLR and pCR was analyzed by using Wilcoxon rank sum test.Results The 3-year overall survival (OS) rates with F-NLR scores of 0,1 and 2 were 72.1％,66.5％ and 50.2％(P=0.010),respectively.The corresponding 3-year disease-free survival (DFS) rates were 64.1％,60.2％ and 45.4％ (P=0.012),respectively.The clinical prognosis of patients with an F-NLR score of 2 was significantly worse compared with those of their counterparts with an F-NLR score of 0-1 (P=0.003).Multivariate analysis demonstrated that the F-NLR score (P=0.004) and TNM stage (P=0.000) were the independent prognostic factors.Conclusions The F-NLR score can be used as an independent prognostic factor for ESCC patients treated with neoadjuvant therapy,which is promising supplement to current TNM staging system,thereby facilitating more accurate risk stratification analysis and achieving individualized multidisciplinary treatment for ESCC patients.

Objective: To compare the effect of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT) on the survival of patients with esophageal cancer. Methods: Clinical data of 275 cases of thoracic esophageal squamous cell carcinoma treated with neoadjuvant therapy combined with surgery from December 2011 to December 2015 were analyzed retrospectively. The data of treatment and follow-up were complete and analyzable. There were 70 cases in the NCRT group and 205 cases in the NCT group. The survival rate was calculated by Kaplan-Meier method and statistically compared by log-rank test, and multivariate analysis was performed by Cox regression model. Results: The median follow-up time was 32(3-84) months. The median survival time and recurrence-free survival time was 42(3-84) months and 30(3-84) months, respectively. The overall 3-and 5-year survival rates were 56.8% and 45.9%, respectively, and the 3-and 5-year recurrence-free survival rates were 45.1% and 38.9%, respectively. The median survival time in the NCRT and NCT groups was 46(7-84) and 40(4-74) months, and the median recurrence-free survival time was 31(3-84) and 28(3-69) months, respectively. The 3-and 5-year overall survival of the two groups were 59.1%, 47.1% and 56.3%, 47.5%(P=0.515), and the 3-and 5-year recurrence-free survival were 44.5%, 40.1% and 47%, 39%, respectively. There was no significant difference in the survival between two neoadjuvant therapy modes (P=0.554). Multivariate analysis showed that postoperative pathological TNM staging was an independent factor affecting the prognosis of patients with esophageal cancer (P=0.001). Conclusions The survival results of NCRT are similar to those of NCT. Postoperative pathological staging is an independent survival factor.

Objective: To perform lymphocyte micronucleus analysis on radiation workers with long-term exposure to low doses ionizing radiation, Evaluate the health condition of radiation workers, and provide the evidence for strengthening surveillance of radiation workers. Methods: From January 1, 2013 to December 21, 2016, a statistical analysis and evaluation was conducted of the peripheral lymphocytes micronucleus rate in 5 901 radiation workers who had undergone medical examinations of employees at Chinese Academy of Medical Sciences Institute of Radiation Medicine. Results: The micronucleus rates in radiation workers of the on-job group were higher than the pre-job group (P<0.01) . Significant difference was found among the different sex (t=5.97) , different types (χ²=378.69) , different levels of work units (χ²=115.48) . Significant difference was found among the micronucleus rates of 672 radiation workers of the on-job group from 2013 to 2016 (χ²=92.57, P<0.01) . Conclusion The peripheral lymphocytes micronucleus rate of radiation workers were significantly higher than non-contact workers. Significant increasing trend of micronucleus rates was noted among the radiation worker with increasing exposure time. The peripheral lymphocytes micronucleus rates of interventional therapy workers were highest. The peripheral lymphocytes micronucleus rates of Private hospitals workers were highest. This phenomenon deserves attention. Protection needs to be strengthened to ensure the health of radiation workers.

Objective To explore the role of radiotherapy in the treatment of primary central nervous system lymphoma. Methods Clinical data of 60 patients diagnosed with primary central nervous system lymphoma from September 2010 to December 2017 were retrospectively analyzed. Among them, 50 cases were diagnosed by histopathological examination after stereotactic biopsy or tumor resection and 10 patients were diagnosed by gadolinium enhanced magnetic resonance imaging ( MRI) . Fifty-two patients underwent chemotherapy, and 45 of them received methotrexate-based chemotherapy, 25 received rituximab-based regimen. Twenty-seven patients were given with planned whole brain radiotherapy, while 33 patients were not. Salvage radiotherapy was delivered in 9 patients after treatment failure. Results The median follow-up time was 28 months ( 5-70 months) . The median overall survival time and median progression-free survival time of the whole patients was 22 months ( 5-65 months) and 13 months ( 5-55 months) , respectively. The 4-year overall survival rate and progression-free survival rate were 61% and 33%, respectively. The 4-year overall survival rates between patients with and without planned whole brain radiotherapy were 68% and 54% ( P=0.083) . The 4-year progression-free survival rates between patients with and without planned whole brain radiotherapy were 47% and 20% ( P=0.014) , respectively. Patients with and without salvage whole brain radiotherapy had a 4-year overall survival of 49% and 68%, respectively ( P=0.398) . Among patients who received whole brain radiotherapy, patients with a lower dose of ≤36 Gy had a similar overall survival compared with those with a higher dose of>36 Gy ( 80% vs. 45%, P=0.136) . Conclusions Radiotherapy is part of the comprehensive treatment of primary central nervous system lymphoma. Planned radiotherapy may bring clinical benefits to patients during the comprehensive therapy. However, the irradiation dose to the whole brain should not be too high because of neurotoxicity.

Objective: To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Methods: From December 2011 to December 2015, 152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed. The overall survival (OS) after treatment failure, clinical efficacy and prognostic factors of different salvage treatments were analyzed. OS was calculated by Kaplan-Meier method. Prognostic analysis was performed by using multivariate Cox regression model. Results: The median interval of the first recurrence was 10.6(2.0 to 69.1) months. The median OS after recurrence was 8.0(0.8 to 43.3) months. The 1-, 2-and 3-year OS rates after recurrence were 36.0%, 15.1% and 5.2%, respectively. The median OS of patients with locoregional recurrence alone, distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months, 6.7(1.2 to 28.6) months and 5.1(0.8 to 22.9) months, respectively. Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009), ypTNM stage (P=0.012), comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma. Conclusions Neoadjuvant therapy, ypTNM stage, recurrence pattern and post-recurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory. After recurrence, combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment.

Objective:To examine the long-term survival outcomes and identify mortality risk factors for coronary artery bypass grafting patients who received venoarterial extracorporeal membrane oxygenation(VA-ECMO) for postcardiotomy cardiogenic shock.Methods:Data from 121 consecutive venoarterial extracorporeal membrane oxygenation-treated coronary artery bypass grafting(CABG) patients at Beijing Anzhen Hospital between June 2012 and December 2016 were analyzed. There were 84 males and 24 females. The median age was 62(55, 67) years, and the median body mass index was 25(23, 27)kg/m 2. Thirty-seven patients(34%) had left main artery disease, and 56 patients(52%) underwent off-pump CABG. According to the 3 year survival outcome after ECMO, patients were divided into survival group(35 cases) and non-survival group(73 cases). The differences of clinical indicators between the two groups were compared and analyzed. Multivariable Cox regression modeling was used to identify factors independently associated with 36 month mortality. Results:Sixty-five patients(60%) could be weaned from VA-ECMO, 49 patients(45%) survived to hospital discharge, and 35 patients(32%) survived to 3 years. The median( IQR) time on VA-ECMO support was 4(3, 5) days. The median( IQR) length of ICU stay and hospital stay duration were 8(5, 12) and 20(13, 29) days, respectively. Older age( HR=1.06, 95% CI: 1.03-1.10, P<0.001), left main coronary artery disease( HR=1.62, 95% CI: 1.00-2.60, P=0.048), and vasoactive inotropic score( HR=1.09, 95% CI: 1.03-1.17, P=0.007)were independent risk factors associated with 3-year mortality. The area under the receiver operating characteristic curve for the model, which was constructed with age≥60years, left main coronary artery disease, and vasoactive inotropic score>60, was 0.88(95% CI: 0.80-0.95). Conclusion:Long-term survival of patients who survive to discharge appears favorable. Older age, left main coronary artery disease, and vasoactive inotropic score were associated with 3-year mortality in coronary artery bypass grafting patients who received VA-ECMO.